Prostate cancer is the second leading of cancer deaths among american men after skin cancer. In African- American men, the incidence of prostate cancer is 65% higher and the mortality rate is more than double compared to Caucasian men. The reasons for this racial disparity in incidence and death rate due to this disease in African-American are poorly understood, but may involve both biological and environmental factors. The Center for Cancer Research and Therapeutic Development at Clark Atlanta University is building a comprehensive research program to investigate the cellular and genetic factors involved in transformation, angiogenesis and metastasis of prostate cancer and how these factors may differ in African- American men. Three research projects in this grant application will investigate 1. Role of TGFbeta signaling during different phases of prostate cancer, 2. Impact of androgen regulated immune/inflammatory pathways in prostate cancers, and 3. The role of SNAIL transcription factor and TGFbeta in bone metastasis of prostate cancer cells. In addition, we are proposing six pilot projects which will focus on different aspects of prostate cancer biology such as: the role of IL-10 in prostate cancer immunity, c-kit ligand and signaling in metastatic cancer cells, role of PI3-kinase isoforms in prostate cancer, chromatin remodeling and its impact in prostate cancer cells, role of sterols in prostate cancer cell proliferation and apoptosis, and development of highly sensitive techniques to detect prostate cancer biomarkers. All investigators are housed in the same building and have access to state-of- the Art research core laboratories. These cores provide instrumentation and technical assistance in cell biology, molecular biology, and imaging. These facilites are managed by a Senior Research Scientist and a Facilites Coordinator. The reagents, clinical samples and materials generated for individual projects will be handled by the research core and will be shared by all investigators. The research projects from individual investigators are based on very interactive approaches and provide opportunities for collaborations among multiple investigators at the Center and scientists at several other institutions. The Pis of different projects and the research staff meets once a week to monitor and discuss the progress of individual projects and the scientific program of the center is overseen by external advisory committees with several members in the area of prostate cancer biology and chemistry.